ObjectiveTo explore the differential expression of Sirtuin1 (SIRT1) in type A aortic dissection at diverse ages.MethodsThe expression of SIRT1 and monocyte chemoattractant protein-1 (MCP-1) in aortic tissue of the patients with type A aortic dissection (an aortic dissection group) and coronary heart disease (a control group) from 2019 to 2020 in the First Hospital of China Medical University was analyzed. In each group, the patients were divided into 3 subgroups according to the age (a younger subgroup, <45 years; a middle age subgroup, 45-60 years; an elderly subgroup, >60 years). The quantitative real-time PCR, Western blotting and immunochemical stainning were used to detect the mRNA or protein expression of SIRT1 and MCP-1. ResultsA total of 60 patients were included in each group, including 79 males and 41 females. There were 20 patients in the yonger, middle age and elderly subgroups for the two groups, respectively. Compared with the control group, the expression of SIRT1 mRNA decreased in the aortic dissection group (the younger subgroup: 4.54±1.52 vs. 8.78±2.57; the middle age group: 2.70±1.50 vs. 5.74±1.07; the elderly group: 1.41±1.33 vs. 3.09±1.14, P<0.001). Meanwhile, SIRT1 mRNA in the aortic dissection group declined with age (P<0.01). Compared with the control group, SIRT1 protein expression decreased significantly in the aortic dissection group (the younger group: 0.64±0.18 vs. 1.18±0.47; the middle age group: 0.43±0.26 vs. 0.69±0.32; the elderly group: 0.31±0.24 vs. 0.45±0.29, P<0.01). The Western blotting results showed that the expression of SIRT1 protein in the aortic dissection group decreased with age (P<0.01). The MCP-1 protein expression of younger and middle age patients in the aortic dissection group was increased compared with that in the control group (the younger group: 0.65±0.27 vs. 0.38±0.22; the middle age group: 1.08±0.30 vs. 0.46±0.36, P<0.001). MCP-1 expression increased with age (P<0.01). The result of immunohistochemical staining for SIRT1 protein was similar to that of Western blotting.ConclusionThe expression of SIRT1 decreases in patients with aortic dissection disease, and declines with age. SIRT1 may play an important role in the treatment and screening of type A aortic dissection.
Cardiovascular disease is a severe threat to human health and life. Among many risk factors of cardiovascular disease, genetic or gene-based ones are drawing more and more attention in recent years. Accumulated evidence has demonstrated that the loss or mutation of ataxia telangiectasia mutated (ATM) gene can result in DNA damage repair dysfunctions, telomere shortening, decreased antioxidant capacity, insulin resistance, increased lipid levels, etc., and thus can promote the occurrence of cardiovascular risk factors, such as aging, atherosclerosis and metabolic syndrome. In this review, we discusses the possible mechanisms between ATM gene and cardiovascular risk factors, which could be helpful to the related research and clinical application.
Atherosclerosis is a complex disease characterized by lipid accumulation in the vascular wall and influenced by multiple genetic and environmental factors. To understand the mechanisms of molecular regulation related to atherosclerosis better, a protein interaction network was constructed in the present study. Genes were collected in nucleotide database and interactions were downloaded from Biomolecular Object Network Database (BOND). The interactional data were imported into the software Cytoscape to construct the interaction network, and then the degree characteristics of the network were analyzed for Hub proteins. Statistical significance pathways and diseases were figured out by inputting Hub proteins to KOBAS2.0. The complete pathway network related to atherosclerosis was constructed. The results identified a series of key genes related to atherosclerosis, which would be the potential promising drug targets for effective prevention.
ObjectiveTo compare mid-to long-term outcomes of selective coronary venous bypass grafting (SCVBG) using internal mammary artery (IMA) grafts and great saphenous vein (GSV) grafts for surgical treatment of diffuse right coronary artery atherosclerosis.
MethodsWe retrospectively analyzed clinical data of 75 patients undergoing SCVBG in Beijing Anzhen Hospital from January 2003 to December 2012. GSV was used as grafts for SCVBG in 54 patients (GSV group), and IMA was used as grafts for SCVBG in 21 patients (IMA group). All the patients were followed up in November 2013. Their survival condition, recent relapse rate of angina, recent echocardiographic results and coronary CT angiography (CTA) were analyzed.
ResultsOverall survival rate of IMA group was slightly higher than that of GSV group (100.0% vs. 83.3%), but survival curves showed no statistical difference in survival rate between the 2 groups (P=0.055). Coronary CTA showed significant blockage in GSV grafts and middle cardiac vein in patients in GSV group (n=39), while IMA grafts and middle cardiac vein in patients in IMA group (n=18) were mostly visible and patent (P < 0.001). Left ventricular ejection fraction (LVEF) of the 2 groups were significantly higher than preoperative values, but there was no statistical difference between the 2 groups.
ConclusionCompared with SCVBG using GSV, SCVBG using IMA can significantly improve mid-to long-term patency of the grafts and middle cardiac vein, and is an efficacious procedure for diffuse right coronary artery atherosclerosis.
Objective To explore the risk factors of carotid artery atherosclerotic plaque in ischemic stroke patients. Methods One hundred and forty-eight patients with ischemic stoke were allocated into two groups by ultrasonographic testing (80 with plaque and 68 without plaque). The carotid artery acoustic densitometry (IMT), blood pressure, blood glucose , blood lipid, fibriongen (FIB), c-reactive protein (CRP) were tested. First, single variable analysis was conducted and then multivariate non-condition stepwise logistic model analysis was conducted. Results Carotid IMT, age , total cholesterol (TC), low density lipoprotein (LDL)-CH, FIB, CRP level and the incidence of hypertension and diabetes were significantly higher in ischemic stroke patients with carotid artery plaques than patients without plaques (P≤0.05); Multiple logistic regression analysis showed the most important risk factors of plaques were CRP (OR=3.546, P=0.035) and FIB (OR=1.074, P=0.012) level. Conclusion The main risk factors of carotid atherosclerosis plaque are almost the same as atherosclerosis, such as age , hypertension ,diabetes, hyperlipidemia , high FIB and CRP level and increase in carotid IMT. CRP and FIB may play a crucial role in the development of carotid artery atherosclerosis plaque.
Atherosclerotic plaque rupture is the main cause of many cardiovascular diseases, and biomechanical factors play an important role in the process of plaque rupture. In the study of plaque biomechanics, there are relatively few studies based on fatigue fracture failure theory, and most of them mainly focus on the whole fatigue propagation process from crack initiation to plaque rupture, while there are few studies on the influence of crack on plaque rupture at a certain time in the process of fatigue propagation. In this paper, a two-dimensional plaque model with crack was established. Based on the theory of fracture mechanics and combined with the finite element numerical simulation method, the stress intensity factor (SIF) and related influencing factors at the crack tip in the plaque were studied. The SIF was used to measure the influence of crack on plaque rupture. The results show that the existence of crack can lead to local stress concentration, which increases the risk of plaque rupture. The SIF at the crack tip in the plaque was positively correlated with blood pressure, but negatively correlated with fibrous cap thickness and lipid pool stiffness. The effect of the thickness and angle of lipid pool on the SIF at the crack tip in the plaque was less than 4%, which could be ignored. This study provides a theoretical basis for the risk assessment of plaque rupture with cracks.
Obesity, sleep disorders, psychological stress, sedentary are modifiable cardiovascular risk factors. There is growing evidence that these risk factors may accelerate the chronic inflammatory process of atherosclerosis and lead to myocardial infarction. Studies on the role of immune cells and their related immune mechanisms in atherosclerosis have shown that the above modifiable risk factors can affect the hematopoiesis of the bone marrow system, affect the production of immune cells and phenotypes, and then affect the progress of atherosclerosis. This review will focus on the effects of modifiable cardiovascular risk factors on the progression of atherosclerosis through the role of the innate immune system.
Objective To investigate the potential causal associations between 731 immune cell traits and atherosclerosis by Mendelian randomization (MR) analysis. Methods Using single nucleotide polymorphisms (SNPs) as instrumental variables, genome-wide association study (GWAS) summary statistics (GCST90001391 to GCST90002121) for 731 immune cell traits were obtained from the GWAS Catalog database, and the atherosclerosis dataset (finn-b-I9_CORATHER) was retrieved from the IEU database for MR analysis. The inverse variance weighted method, MR-Egger regression, weighted median, simple mode, and weighted mode approaches were employed to estimate the causal effects between the 731 immune cell traits and atherosclerosis, using odds ratio (OR) with 95% confidence interval (CI) as the effect size. Cochran Q test was used to assess heterogeneity. Horizontal pleiotropy was evaluated using the MR-Egger intercept test and the MR-PRESSO method. Leave-one-out analysis was conducted to examine the sensitivity of the causal estimates to individual SNPs. Results MR analysis revealed potential causal associations between 24 immune cell traits and atherosclerosis (P<0.05). Among them, human leucocyte antigen (HLA)-DR on plasmacytoid dendritic cells (DC) [OR=1.035, 95%CI (1.016, 1.054), P<0.001] and hematopoietic stem cell absolute count (HSCAC) [OR=1.049, 95%CI (1.021, 1.077), P<0.001] showed significant positive causal associations with atherosclerosis (P≤0.001), whereas CD86 on CD62L+ myeloid DC [OR=0.953, 95%CI (0.926, 0.981), P=0.001] exhibited a significant negative causal association with atherosclerosis (P≤0.001). The results of Cochran Q test, MR-Egger regression, and MR-PRESSO indicated P-values>0.05, suggesting no evidence of heterogeneity or horizontal pleiotropy in the causal estimates for these three immune cell traits. Reverse MR analysis, using the 24 immune cell traits as outcome variables, showed no evidence of causal association (P>0.05), supporting a unidirectional causal relationship from immune cells to atherosclerosis. Conclusion HLA-DR on plasmacytoid DC and HSCAC may serve as risk factors for atherosclerosis, while CD86 on CD62L+ myeloid DC may play a protective role against atherosclerosis.
Objective To investigate the predictive factors of clinical progression and short-term prognosis of cerebral infarction caused by large artery atherosclerosis (LAA). MethodsPatients with acute LAA cerebral infarction who were hospitalized in the Department of Neurology, Lianyungang Hospital of Traditional Chinese Medicine between January 2016 and May 2019 were included. On admission, the patients’ medical history was collected. The degree of neurological deficit was assessed, blood pressure, blood glucose, blood lipids, plasma homocysteine, lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured, and intracranial and extracranial blood vessels related test results were collected. Within 72 hours of onset, the Scandinavian Stroke Scale (SSS) was used to determine whether the patients’ condition progressed. The modified Rankin scale was used to evaluate the short-term prognosis at 30 days of onset. The related factors of clinical progression and short-term prognosis of LAA cerebral infarction were analyzed. Results Finally, 100 patients were included. According to the SSS assessment results within 72 hours of onset, 27 cases were divided into the progression group and 73 cases in the non-progression group. There was no significant difference in gender and age between the two groups (P>0.05). According to the evaluation results of the modified Rankin scale at 30 days of onset, they were divided into 31 cases in the poor prognosis group and 69 cases in the good prognosis group. There was no significant difference in gender and age between the two groups (P>0.05). Logistic regression analysis showed that plasma Lp-PLA2 [odds ratio (OR)=1.013, 95% confidence interval (CI) (1.007, 1.018), P<0.001], SSS score [OR=0.910, 95%CI (0.842, 0.985), P=0.019], and history of hypertension [OR=5.527, 95%CI (1.241, 24.613), P=0.025] were the predictors of disease progression within 72 hours. SSS score [OR=0.849, 95%CI (0.744, 0.930), P<0.001], carotid artery stenosis [OR=9.536, 95%CI (1.395, 65.169), P=0.021] and progressive stroke [OR=8.873, 95%CI (1.937, 40.640), P=0.005] were the predictors of short-term prognosis of LAA cerebral infarction. Conclusions History of hypertension and high levels of plasma Lp-PLA2 are predictors of early progression of cerebral infarction. Carotid artery stenosis and progressive stroke are predictors of adverse outcomes in the acute phase of cerebral infarction. Neurological scores on admission was a predictor for short-term adverse outcomes in the early and acute phases.
ObjectiveTo explore the association of elongase of very long chain fatty acids family member 6 (ELOVL6) gene with increased risk of large-artery atherosclerosis stroke (LAA) in Han Chinese population in Chengdu.MethodsHan Chinese populations in Chengdu, Sichuan were chosen for this study using the case-control design between January 2015 and December 2017. The genotypes and haplotypes of six single nucleotides polymorphisms (SNPs) of ELOVL6 gene (rs3813825, rs17041272, rs4141123, rs9997926, rs6824447, and rs12504538) were analyzed in different genetic models in entire samples, and gene-enviromental interaction analyses were also carried out to get an insight of the risk factors for LAA. At the same time, we also analyzed the gene expression profile in peripheral blood mononuclear cells between groups.ResultsA total of 240 LAA cases and 211 healthy controls were enrolled in this study. All the enrolled subjects presented CC genotype of rs9997926, while the other five SNPs (rs3813825, rs17041272, rs4141123, rs6824447, and rs12504538) were genotyped successfully in all the enrolled subjects. rs17041272 polymorphism and TGTTG haplotype were significantly associated with LAA risk in studied population [CC/(CG+GG): odds ratio (OR)=0.640, 95% confidence interval (CI) (0.423, 0.968), P=0.034; TGTTG: OR=1.776, 95%CI (1.069, 2.951), P=0.024], and the interaction among rs17041272, rs6824447 SNPs and dyslipidemia increased susceptibility to LAA [OR=2.737, 95%CI (1.715, 4.368), P<0.001]. The ELOVL6 gene expression level was higher in LAA subjects (t=?3.167, P=0.003).ConclusionsELOVL6 gene is associated with LAA risk in Han nationality of Chinese population in Chengdu, and the interaction of gene-environmental risk factors could be of great importance in pathophysiology of LAA.
